Gonorrhea pathophysiology: Difference between revisions

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==Overview==
==Overview==
Gonorrhea is a sexually transmitted disease (STD) that is caused by ''[[Neisseria gonorrhea]]''.
Gonorrhea is a sexually transmitted disease (STD) caused by ''[[Neisseria gonorrhea]]''.
It can infect mucus-secreting epithelial cells both in men and women.
It can infect mucus-secreting [[epithelial cells]] both in men and women.
The recognized routes of transmission of the ''[[Neisseria gonorrhoeae]]'' include vaginal intercourse, rectal intercourse, fellatio, cunnilingus, and [[perinatal]].
Established routes of transmission of the ''[[Neisseria gonorrhoeae]]'' bacterium include vaginal intercourse, rectal intercourse, fellatio, cunnilingus, and [[perinatal]].
The main pathogenicity of the ''[[Neisseria gonorrhea]]'' obtains from the attachment ability of the [[pili|surface pili]] to the surface of the [[urethra]], [[fallopian tubes]] and [[endocervix]].<ref name="pmid4958881">{{cite journal| author=Sparling PF| title=Genetic transformation of Neisseria gonorrhoeae to streptomycin resistance. | journal=J Bacteriol | year= 1966 | volume= 92 | issue= 5 | pages= 1364-71 | pmid=4958881 | doi= | pmc=276432 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=4958881  }} </ref><ref name="pmid4631989">{{cite journal| author=Swanson J| title=Studies on gonococcus infection. IV. Pili: their role in attachment of gonococci to tissue culture cells. | journal=J Exp Med | year= 1973 | volume= 137 | issue= 3 | pages= 571-89 | pmid=4631989 | doi= | pmc=2139381 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=4631989  }} </ref><ref name="pmid9701824">{{cite journal| author=Wolfgang M, Lauer P, Park HS, Brossay L, Hébert J, Koomey M| title=PilT mutations lead to simultaneous defects in competence for natural transformation and twitching motility in piliated Neisseria gonorrhoeae. | journal=Mol Microbiol | year= 1998 | volume= 29 | issue= 1 | pages= 321-30 | pmid=9701824 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9701824  }} </ref>
The main pathogenicity of the ''[[Neisseria gonorrhea]]'' stems from the ability of its [[pili|surface pili]] to attach to the surface of the [[urethra]], [[fallopian tubes]], and [[endocervix]].<ref name="pmid4958881">{{cite journal| author=Sparling PF| title=Genetic transformation of Neisseria gonorrhoeae to streptomycin resistance. | journal=J Bacteriol | year= 1966 | volume= 92 | issue= 5 | pages= 1364-71 | pmid=4958881 | doi= | pmc=276432 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=4958881  }} </ref><ref name="pmid4631989">{{cite journal| author=Swanson J| title=Studies on gonococcus infection. IV. Pili: their role in attachment of gonococci to tissue culture cells. | journal=J Exp Med | year= 1973 | volume= 137 | issue= 3 | pages= 571-89 | pmid=4631989 | doi= | pmc=2139381 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=4631989  }} </ref><ref name="pmid9701824">{{cite journal| author=Wolfgang M, Lauer P, Park HS, Brossay L, Hébert J, Koomey M| title=PilT mutations lead to simultaneous defects in competence for natural transformation and twitching motility in piliated Neisseria gonorrhoeae. | journal=Mol Microbiol | year= 1998 | volume= 29 | issue= 1 | pages= 321-30 | pmid=9701824 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9701824  }} </ref>
Anotehr virulence factors of gonorrhea is [[porin]]. two main porin serotypes include PorB.1A strains (resulting in a disseminated gonococcal infection) and PorB.1B strains (resulting in local genital infections).<ref name="pmid6407021">{{cite journal| author=Young JD, Blake M, Mauro A, Cohn ZA| title=Properties of the major outer membrane protein from Neisseria gonorrhoeae incorporated into model lipid membranes. | journal=Proc Natl Acad Sci U S A | year= 1983 | volume= 80 | issue= 12 | pages= 3831-5 | pmid=6407021 | doi= | pmc=394146 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6407021  }} </ref><ref name="pmid11157049">{{cite journal| author=Ram S, Cullinane M, Blom AM, Gulati S, McQuillen DP, Monks BG et al.| title=Binding of C4b-binding protein to porin: a molecular mechanism of serum resistance of Neisseria gonorrhoeae. | journal=J Exp Med | year= 2001 | volume= 193 | issue= 3 | pages= 281-95 | pmid=11157049 | doi= | pmc=2195916 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11157049  }} </ref><ref name="pmid9705949">{{cite journal| author=Ram S, McQuillen DP, Gulati S, Elkins C, Pangburn MK, Rice PA| title=Binding of complement factor H to loop 5 of porin protein 1A: a molecular mechanism of serum resistance of nonsialylated Neisseria gonorrhoeae. | journal=J Exp Med | year= 1998 | volume= 188 | issue= 4 | pages= 671-80 | pmid=9705949 | doi= | pmc=2213355 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9705949  }} </ref>
Anotehr virulence factor of gonorrhea is [[porin]]. The two main porin serotypes include PorB.1A strains (resulting in a disseminated gonococcal infection) and PorB.1B strains (resulting in local genital infections).<ref name="pmid6407021">{{cite journal| author=Young JD, Blake M, Mauro A, Cohn ZA| title=Properties of the major outer membrane protein from Neisseria gonorrhoeae incorporated into model lipid membranes. | journal=Proc Natl Acad Sci U S A | year= 1983 | volume= 80 | issue= 12 | pages= 3831-5 | pmid=6407021 | doi= | pmc=394146 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6407021  }} </ref><ref name="pmid11157049">{{cite journal| author=Ram S, Cullinane M, Blom AM, Gulati S, McQuillen DP, Monks BG et al.| title=Binding of C4b-binding protein to porin: a molecular mechanism of serum resistance of Neisseria gonorrhoeae. | journal=J Exp Med | year= 2001 | volume= 193 | issue= 3 | pages= 281-95 | pmid=11157049 | doi= | pmc=2195916 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11157049  }} </ref><ref name="pmid9705949">{{cite journal| author=Ram S, McQuillen DP, Gulati S, Elkins C, Pangburn MK, Rice PA| title=Binding of complement factor H to loop 5 of porin protein 1A: a molecular mechanism of serum resistance of nonsialylated Neisseria gonorrhoeae. | journal=J Exp Med | year= 1998 | volume= 188 | issue= 4 | pages= 671-80 | pmid=9705949 | doi= | pmc=2213355 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9705949  }} </ref>


In '''pregnancy''', gonococcus can be transmitted to the fetus at the time of delivery. This results in infection of the [[Neonatal Conjunctivitis|conjuctiva]]. This appears 1 to 4 days after birth as severe discharge with marked swelling and redness of the eyelids and conjunctiva.
In '''pregnancy''', gonococcus can be transmitted to the fetus at the time of delivery. This results in infection of the [[Neonatal Conjunctivitis|conjuctiva]]. This appears 1 to 4 days after birth as severe discharge with marked swelling and redness of the eyelids and conjunctiva.
Additionally, development of '''disseminated gonococcal infection''' is the result of ''Neisserial'' organisms dissemination to the blood due to a variety of predisposing factors, such as change in PH, pregnancy, menstruation, PorB.1A strains, and complement deficiencies.<ref name=DGI>WATRING, WATSON G., and DANIEL L. VAUGHN. "Gonococcemia in pregnancy." Obstetrics & Gynecology 48.4 (1976): 428-430.</ref><ref name=DGI-2> Angulo, Juan M., and Luis R. Espinoza. "Gonococcal arthritis." Comprehensive therapy 25.3 (1999): 155-162.</ref><ref name="pmid3088132">{{cite journal| author=Bohnhoff M, Morello JA, Lerner SA| title=Auxotypes, penicillin susceptibility, and serogroups of Neisseria gonorrhoeae from disseminated and uncomplicated infections. | journal=J Infect Dis | year= 1986 | volume= 154 | issue= 2 | pages= 225-30 | pmid=3088132 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3088132  }} </ref><ref name="pmid6415361">{{cite journal| author=O'Brien JP, Goldenberg DL, Rice PA| title=Disseminated gonococcal infection: a prospective analysis of 49 patients and a review of pathophysiology and immune mechanisms. | journal=Medicine (Baltimore) | year= 1983 | volume= 62 | issue= 6 | pages= 395-406 | pmid=6415361 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6415361  }} </ref>
Additionally, development of '''disseminated gonococcal infection''' is the result of ''Neisserial'' organisms' dissemination into the blood due to a variety of predisposing factors such as change in PH, pregnancy, menstruation, PorB.1A strains, and complement deficiencies.<ref name=DGI>WATRING, WATSON G., and DANIEL L. VAUGHN. "Gonococcemia in pregnancy." Obstetrics & Gynecology 48.4 (1976): 428-430.</ref><ref name=DGI-2> Angulo, Juan M., and Luis R. Espinoza. "Gonococcal arthritis." Comprehensive therapy 25.3 (1999): 155-162.</ref><ref name="pmid3088132">{{cite journal| author=Bohnhoff M, Morello JA, Lerner SA| title=Auxotypes, penicillin susceptibility, and serogroups of Neisseria gonorrhoeae from disseminated and uncomplicated infections. | journal=J Infect Dis | year= 1986 | volume= 154 | issue= 2 | pages= 225-30 | pmid=3088132 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3088132  }} </ref><ref name="pmid6415361">{{cite journal| author=O'Brien JP, Goldenberg DL, Rice PA| title=Disseminated gonococcal infection: a prospective analysis of 49 patients and a review of pathophysiology and immune mechanisms. | journal=Medicine (Baltimore) | year= 1983 | volume= 62 | issue= 6 | pages= 395-406 | pmid=6415361 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6415361  }} </ref>


==Pathophysiology==
==Pathophysiology==
Gonorrhea is a sexually transmitted disease (STD) that is caused by ''[[Neisseria gonorrhea]]''.
Gonorrhea is a sexually transmitted disease (STD) that is caused by ''[[Neisseria gonorrhea]]'', a [[gram-negative]] intracellular diplococcus, oxidase-positive bacterium that utilizes glucose, but not sucrose, maltose, or lactose.
''[[Neisseria gonorrhea]]'' is [[gram-negative]] intracellular diplococcus, oxidase-positive, utilizes glucose, but not sucrose, maltose, or lactose.
It can infect mucus-secreting [[epithelial cells]] in both men and women.
It can infect mucus-secreting epithelial cells both in men and women.
===Transmission===
===Transmission===
The recognized routes of transmission of the ''[[Neisseria gonorrhoeae]]'' include:
Established routes of transmission of the ''[[Neisseria gonorrhoeae]]'' include:
*Male to female via [[semen]] (transmission rate is estimated to be  50%-70% per episode)  
*Male to female via [[semen]] (transmission rate is estimated to be  50%-70% per episode)  
*Female vagina to male urethra (transmission rate is estimated to be 20% per episode)
*Female vagina to male urethra (transmission rate is estimated to be 20% per episode)
*Rectal intercourse  
*Rectal intercourse  
*Fellatio and less commonly cunnilingus can result in pharyngeal gonorrhea
*Fellatio and, less commonly, cunnilingus can result in pharyngeal gonorrhea
*[[Perinatal]]
*[[Perinatal]]
===Virulence factors===
===Virulence factors===
The recognized virulence factors of the ''[[Neisseria gonorrhoeae]]'' include:
Established virulence factors of ''[[Neisseria gonorrhoeae]]'' include:
*The main pathogenicity of the ''[[Neisseria gonorrhea]]'' obtains from the [[pili|surface pili]] by following mechanisms:<ref name="pmid4958881">{{cite journal| author=Sparling PF| title=Genetic transformation of Neisseria gonorrhoeae to streptomycin resistance. | journal=J Bacteriol | year= 1966 | volume= 92 | issue= 5 | pages= 1364-71 | pmid=4958881 | doi= | pmc=276432 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=4958881  }} </ref><ref name="pmid4631989">{{cite journal| author=Swanson J| title=Studies on gonococcus infection. IV. Pili: their role in attachment of gonococci to tissue culture cells. | journal=J Exp Med | year= 1973 | volume= 137 | issue= 3 | pages= 571-89 | pmid=4631989 | doi= | pmc=2139381 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=4631989  }} </ref><ref name="pmid9701824">{{cite journal| author=Wolfgang M, Lauer P, Park HS, Brossay L, Hébert J, Koomey M| title=PilT mutations lead to simultaneous defects in competence for natural transformation and twitching motility in piliated Neisseria gonorrhoeae. | journal=Mol Microbiol | year= 1998 | volume= 29 | issue= 1 | pages= 321-30 | pmid=9701824 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9701824  }} </ref>
*The main pathogenicity of the ''[[Neisseria gonorrhea]]'' stems from the [[pili|surface pili]] by following mechanisms:<ref name="pmid4958881">{{cite journal| author=Sparling PF| title=Genetic transformation of Neisseria gonorrhoeae to streptomycin resistance. | journal=J Bacteriol | year= 1966 | volume= 92 | issue= 5 | pages= 1364-71 | pmid=4958881 | doi= | pmc=276432 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=4958881  }} </ref><ref name="pmid4631989">{{cite journal| author=Swanson J| title=Studies on gonococcus infection. IV. Pili: their role in attachment of gonococci to tissue culture cells. | journal=J Exp Med | year= 1973 | volume= 137 | issue= 3 | pages= 571-89 | pmid=4631989 | doi= | pmc=2139381 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=4631989  }} </ref><ref name="pmid9701824">{{cite journal| author=Wolfgang M, Lauer P, Park HS, Brossay L, Hébert J, Koomey M| title=PilT mutations lead to simultaneous defects in competence for natural transformation and twitching motility in piliated Neisseria gonorrhoeae. | journal=Mol Microbiol | year= 1998 | volume= 29 | issue= 1 | pages= 321-30 | pmid=9701824 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9701824  }} </ref>
**Mediate attachment to the surface of the [[urethra]], [[fallopian tubes]] and [[endocervix]]  
**Mediate attachment to the surface of the [[urethra]], [[fallopian tubes]], and [[endocervix]]  
**Preventing [[phagocytosis]] by [[neutrophils]]
**Preventing [[phagocytosis]] by [[neutrophils]]
*Opa proteins (opacity-associated protein) is a surface proteins that helps gonococcus binds to receptors on immune cells<ref name="pmid8113683">{{cite journal| author=Jerse AE, Cohen MS, Drown PM, Whicker LG, Isbey SF, Seifert HS et al.| title=Multiple gonococcal opacity proteins are expressed during experimental urethral infection in the male. | journal=J Exp Med | year= 1994 | volume= 179 | issue= 3 | pages= 911-20 | pmid=8113683 | doi= | pmc=2191399 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8113683  }} </ref><ref name="pmid11850628">{{cite journal| author=Boulton IC, Gray-Owen SD| title=Neisserial binding to CEACAM1 arrests the activation and proliferation of CD4+ T lymphocytes. | journal=Nat Immunol | year= 2002 | volume= 3 | issue= 3 | pages= 229-36 | pmid=11850628 | doi=10.1038/ni769 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11850628  }} </ref><ref name="pmid15972507">{{cite journal| author=Pantelic M, Kim YJ, Bolland S, Chen I, Shively J, Chen T| title=Neisseria gonorrhoeae kills carcinoembryonic antigen-related cellular adhesion molecule 1 (CD66a)-expressing human B cells and inhibits antibody production. | journal=Infect Immun | year= 2005 | volume= 73 | issue= 7 | pages= 4171-9 | pmid=15972507 | doi=10.1128/IAI.73.7.4171-4179.2005 | pmc=1168567 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15972507  }} </ref>
*Opa proteins (opacity-associated protein) are surface proteins that help gonococcus binds to receptors on [[immune cells]]<ref name="pmid8113683">{{cite journal| author=Jerse AE, Cohen MS, Drown PM, Whicker LG, Isbey SF, Seifert HS et al.| title=Multiple gonococcal opacity proteins are expressed during experimental urethral infection in the male. | journal=J Exp Med | year= 1994 | volume= 179 | issue= 3 | pages= 911-20 | pmid=8113683 | doi= | pmc=2191399 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8113683  }} </ref><ref name="pmid11850628">{{cite journal| author=Boulton IC, Gray-Owen SD| title=Neisserial binding to CEACAM1 arrests the activation and proliferation of CD4+ T lymphocytes. | journal=Nat Immunol | year= 2002 | volume= 3 | issue= 3 | pages= 229-36 | pmid=11850628 | doi=10.1038/ni769 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11850628  }} </ref><ref name="pmid15972507">{{cite journal| author=Pantelic M, Kim YJ, Bolland S, Chen I, Shively J, Chen T| title=Neisseria gonorrhoeae kills carcinoembryonic antigen-related cellular adhesion molecule 1 (CD66a)-expressing human B cells and inhibits antibody production. | journal=Infect Immun | year= 2005 | volume= 73 | issue= 7 | pages= 4171-9 | pmid=15972507 | doi=10.1128/IAI.73.7.4171-4179.2005 | pmc=1168567 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15972507  }} </ref>
**Down-regulate activated CD4 cells (prevent an Immune response)
**Down-regulate activated [[CD4+ T cells]] (prevent an [[immune response]])
**Inhibit B-cell antibody production (unable [[immunological memory]] against gonorrhea)
**Inhibit [[B-cell]] antibody production (unable to establish [[immunological memory]] against gonorrhea)
*[[Porin]], two main serotypes have been identified:<ref name="pmid6407021">{{cite journal| author=Young JD, Blake M, Mauro A, Cohn ZA| title=Properties of the major outer membrane protein from Neisseria gonorrhoeae incorporated into model lipid membranes. | journal=Proc Natl Acad Sci U S A | year= 1983 | volume= 80 | issue= 12 | pages= 3831-5 | pmid=6407021 | doi= | pmc=394146 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6407021  }} </ref><ref name="pmid11157049">{{cite journal| author=Ram S, Cullinane M, Blom AM, Gulati S, McQuillen DP, Monks BG et al.| title=Binding of C4b-binding protein to porin: a molecular mechanism of serum resistance of Neisseria gonorrhoeae. | journal=J Exp Med | year= 2001 | volume= 193 | issue= 3 | pages= 281-95 | pmid=11157049 | doi= | pmc=2195916 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11157049  }} </ref><ref name="pmid9705949">{{cite journal| author=Ram S, McQuillen DP, Gulati S, Elkins C, Pangburn MK, Rice PA| title=Binding of complement factor H to loop 5 of porin protein 1A: a molecular mechanism of serum resistance of nonsialylated Neisseria gonorrhoeae. | journal=J Exp Med | year= 1998 | volume= 188 | issue= 4 | pages= 671-80 | pmid=9705949 | doi= | pmc=2213355 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9705949  }} </ref>
*[[Porin]], two main serotypes of which have been identified:<ref name="pmid6407021">{{cite journal| author=Young JD, Blake M, Mauro A, Cohn ZA| title=Properties of the major outer membrane protein from Neisseria gonorrhoeae incorporated into model lipid membranes. | journal=Proc Natl Acad Sci U S A | year= 1983 | volume= 80 | issue= 12 | pages= 3831-5 | pmid=6407021 | doi= | pmc=394146 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6407021  }} </ref><ref name="pmid11157049">{{cite journal| author=Ram S, Cullinane M, Blom AM, Gulati S, McQuillen DP, Monks BG et al.| title=Binding of C4b-binding protein to porin: a molecular mechanism of serum resistance of Neisseria gonorrhoeae. | journal=J Exp Med | year= 2001 | volume= 193 | issue= 3 | pages= 281-95 | pmid=11157049 | doi= | pmc=2195916 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11157049  }} </ref><ref name="pmid9705949">{{cite journal| author=Ram S, McQuillen DP, Gulati S, Elkins C, Pangburn MK, Rice PA| title=Binding of complement factor H to loop 5 of porin protein 1A: a molecular mechanism of serum resistance of nonsialylated Neisseria gonorrhoeae. | journal=J Exp Med | year= 1998 | volume= 188 | issue= 4 | pages= 671-80 | pmid=9705949 | doi= | pmc=2213355 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9705949  }} </ref>
**PorB.1A strains  
**PorB.1A strains  
***Bind to complement inhibitory molecules and resulting in a diminished inflammatory response (disseminated gonococcal infection)
***Bind to complement inhibitory molecules, resulting in a diminished [[inflammatory response]] (disseminated gonococcal infection)
**PorB.1B strains  
**PorB.1B strains  
***Cause local genital infections only
***Cause local genital infections only
Line 41: Line 40:
**LOS binds to human asialoglycoprotein receptor (ASGP-R) expressed on [[sperm cells]] and [[epithelial cells|urethral epithelial cells]]  
**LOS binds to human asialoglycoprotein receptor (ASGP-R) expressed on [[sperm cells]] and [[epithelial cells|urethral epithelial cells]]  
*Gonococcal ribosomal protein L12<ref name="pmid10948117">{{cite journal| author=Spence JM, Clark VL| title=Role of ribosomal protein L12 in gonococcal invasion of Hec1B cells. | journal=Infect Immun | year= 2000 | volume= 68 | issue= 9 | pages= 5002-10 | pmid=10948117 | doi= | pmc=101722 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10948117  }} </ref><ref name="pmid20227765">{{cite journal| author=Tsampalas M, Gridelet V, Berndt S, Foidart JM, Geenen V, Perrier d'Hauterive S| title=Human chorionic gonadotropin: a hormone with immunological and angiogenic properties. | journal=J Reprod Immunol | year= 2010 | volume= 85 | issue= 1 | pages= 93-8 | pmid=20227765 | doi=10.1016/j.jri.2009.11.008 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20227765  }} </ref>
*Gonococcal ribosomal protein L12<ref name="pmid10948117">{{cite journal| author=Spence JM, Clark VL| title=Role of ribosomal protein L12 in gonococcal invasion of Hec1B cells. | journal=Infect Immun | year= 2000 | volume= 68 | issue= 9 | pages= 5002-10 | pmid=10948117 | doi= | pmc=101722 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10948117  }} </ref><ref name="pmid20227765">{{cite journal| author=Tsampalas M, Gridelet V, Berndt S, Foidart JM, Geenen V, Perrier d'Hauterive S| title=Human chorionic gonadotropin: a hormone with immunological and angiogenic properties. | journal=J Reprod Immunol | year= 2010 | volume= 85 | issue= 1 | pages= 93-8 | pmid=20227765 | doi=10.1016/j.jri.2009.11.008 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20227765  }} </ref>
**allows attachment to and invasion of an endometrial cell line via interaction with the lutropin receptor (LHr) which lead to [[pelvic inflammatory disease|pelvic inflammatory disease (PID]]) or disseminated gonococcal infection (DGI) in women
**Allows attachment to and invasion of an endometrial cell line via interaction with the lutropin receptor (LHr), which lead to [[pelvic inflammatory disease|pelvic inflammatory disease (PID]]) or disseminated gonococcal infection (DGI) in women
*Release of IgA1 proteases<ref name="pmid9220014">{{cite journal| author=Lin L, Ayala P, Larson J, Mulks M, Fukuda M, Carlsson SR et al.| title=The Neisseria type 2 IgA1 protease cleaves LAMP1 and promotes survival of bacteria within epithelial cells. | journal=Mol Microbiol | year= 1997 | volume= 24 | issue= 5 | pages= 1083-94 | pmid=9220014 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9220014  }} </ref><ref name="pmid21734909">{{cite journal| author=Hobbs MM, Sparling PF, Cohen MS, Shafer WM, Deal CD, Jerse AE| title=Experimental Gonococcal Infection in Male Volunteers: Cumulative Experience with Neisseria gonorrhoeae Strains FA1090 and MS11mkC. | journal=Front Microbiol | year= 2011 | volume= 2 | issue=  | pages= 123 | pmid=21734909 | doi=10.3389/fmicb.2011.00123 | pmc=3119411 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21734909  }} </ref>
*Release of IgA1 [[proteases]]<ref name="pmid9220014">{{cite journal| author=Lin L, Ayala P, Larson J, Mulks M, Fukuda M, Carlsson SR et al.| title=The Neisseria type 2 IgA1 protease cleaves LAMP1 and promotes survival of bacteria within epithelial cells. | journal=Mol Microbiol | year= 1997 | volume= 24 | issue= 5 | pages= 1083-94 | pmid=9220014 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9220014  }} </ref><ref name="pmid21734909">{{cite journal| author=Hobbs MM, Sparling PF, Cohen MS, Shafer WM, Deal CD, Jerse AE| title=Experimental Gonococcal Infection in Male Volunteers: Cumulative Experience with Neisseria gonorrhoeae Strains FA1090 and MS11mkC. | journal=Front Microbiol | year= 2011 | volume= 2 | issue=  | pages= 123 | pmid=21734909 | doi=10.3389/fmicb.2011.00123 | pmc=3119411 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21734909  }} </ref>
**The exact pathogenesis is not fully understood. It is though that IgA protease may play a role gonococcal infection in women
**The exact pathogenesis is not fully understood, but it is thought that IgA protease may play a role gonococcal infection in women


In '''pregnancy''', gonococcus can be transmitted to the fetus at the time of delivery. This results in infection of the [[Neonatal Conjunctivitis|conjuctiva]]. This appears 1 to 4 days after birth as severe discharge with marked swelling and redness of the eyelids and conjunctiva.
In '''pregnancy''', gonococcus can be transmitted to the fetus at the time of delivery. This results in infection of the [[Neonatal Conjunctivitis|conjuctiva]]. This appears 1 to 4 days after birth as severe discharge with marked swelling and redness of the eyelids and conjunctiva.


Development of '''disseminated gonococcal infection''' is the result of Neisserial organisms dissemination to the blood due to a variety of predisposing factors, such as:<ref name=DGI>WATRING, WATSON G., and DANIEL L. VAUGHN. "Gonococcemia in pregnancy." Obstetrics & Gynecology 48.4 (1976): 428-430.</ref><ref name=DGI-2> Angulo, Juan M., and Luis R. Espinoza. "Gonococcal arthritis." Comprehensive therapy 25.3 (1999): 155-162.</ref><ref name="pmid3088132">{{cite journal| author=Bohnhoff M, Morello JA, Lerner SA| title=Auxotypes, penicillin susceptibility, and serogroups of Neisseria gonorrhoeae from disseminated and uncomplicated infections. | journal=J Infect Dis | year= 1986 | volume= 154 | issue= 2 | pages= 225-30 | pmid=3088132 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3088132  }} </ref><ref name="pmid6415361">{{cite journal| author=O'Brien JP, Goldenberg DL, Rice PA| title=Disseminated gonococcal infection: a prospective analysis of 49 patients and a review of pathophysiology and immune mechanisms. | journal=Medicine (Baltimore) | year= 1983 | volume= 62 | issue= 6 | pages= 395-406 | pmid=6415361 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6415361  }} </ref>
Development of '''disseminated gonococcal infection''' is the result of ''Neisserial'' organisms' dissemination into the blood due to a variety of predisposing factors such as:<ref name=DGI>WATRING, WATSON G., and DANIEL L. VAUGHN. "Gonococcemia in pregnancy." Obstetrics & Gynecology 48.4 (1976): 428-430.</ref><ref name=DGI-2> Angulo, Juan M., and Luis R. Espinoza. "Gonococcal arthritis." Comprehensive therapy 25.3 (1999): 155-162.</ref><ref name="pmid3088132">{{cite journal| author=Bohnhoff M, Morello JA, Lerner SA| title=Auxotypes, penicillin susceptibility, and serogroups of Neisseria gonorrhoeae from disseminated and uncomplicated infections. | journal=J Infect Dis | year= 1986 | volume= 154 | issue= 2 | pages= 225-30 | pmid=3088132 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3088132  }} </ref><ref name="pmid6415361">{{cite journal| author=O'Brien JP, Goldenberg DL, Rice PA| title=Disseminated gonococcal infection: a prospective analysis of 49 patients and a review of pathophysiology and immune mechanisms. | journal=Medicine (Baltimore) | year= 1983 | volume= 62 | issue= 6 | pages= 395-406 | pmid=6415361 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6415361  }} </ref>
*Host factors
*Host factors
**Change In PH
**Change in pH
***Pregnancy  
***Pregnancy  
***Menstruation  
***Menstruation  
Line 60: Line 59:
===Host Factors===
===Host Factors===
Host factors play an important role in mediating entry of gonococci into nonphagocytic cells by following methods:<ref name="pmid19414800">{{cite journal| author=Duncan JA, Gao X, Huang MT, O'Connor BP, Thomas CE, Willingham SB et al.| title=Neisseria gonorrhoeae activates the proteinase cathepsin B to mediate the signaling activities of the NLRP3 and ASC-containing inflammasome. | journal=J Immunol | year= 2009 | volume= 182 | issue= 10 | pages= 6460-9 | pmid=19414800 | doi=10.4049/jimmunol.0802696 | pmc=2722440 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19414800  }} </ref><ref name="pmid9857075">{{cite journal| author=Mosleh IM, Huber LA, Steinlein P, Pasquali C, Günther D, Meyer TF| title=Neisseria gonorrhoeae porin modulates phagosome maturation. | journal=J Biol Chem | year= 1998 | volume= 273 | issue= 52 | pages= 35332-8 | pmid=9857075 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9857075  }} </ref>
Host factors play an important role in mediating entry of gonococci into nonphagocytic cells by following methods:<ref name="pmid19414800">{{cite journal| author=Duncan JA, Gao X, Huang MT, O'Connor BP, Thomas CE, Willingham SB et al.| title=Neisseria gonorrhoeae activates the proteinase cathepsin B to mediate the signaling activities of the NLRP3 and ASC-containing inflammasome. | journal=J Immunol | year= 2009 | volume= 182 | issue= 10 | pages= 6460-9 | pmid=19414800 | doi=10.4049/jimmunol.0802696 | pmc=2722440 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19414800  }} </ref><ref name="pmid9857075">{{cite journal| author=Mosleh IM, Huber LA, Steinlein P, Pasquali C, Günther D, Meyer TF| title=Neisseria gonorrhoeae porin modulates phagosome maturation. | journal=J Biol Chem | year= 1998 | volume= 273 | issue= 52 | pages= 35332-8 | pmid=9857075 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9857075  }} </ref>
#N. gonorrhea activates phosphatidylcholine specific phospholipase C and acidic sphingomyelinase and release of diacylglycerol and [[ceramide]].
#''N. gonorrhea'' activates phosphatidylcholine specific [[phospholipase C]] and acidic [[sphingomyelinase]] and release of [[diacylglycerol]] and [[ceramide]]
#Accumulation of ceramide results in [[apoptosis]]
#Accumulation of ceramide results in [[apoptosis]]
#[[Apoptosis]] may cause disruption of epithelial integrity  
#[[Apoptosis]] may cause disruption of epithelial integrity  
#Disturbed epithelium facilitate entry of gonococci into sub [[epithelial tissue]]
#Disturbed [[epithelium]] facilitate entry of gonococci into sub [[epithelial tissue]]
*Additionally, gonococcus can survive in [[neutrophils]] and [[macrophages]] by preventing the formation of degradative phagolysosomes<ref name="pmid23374609">{{cite journal| author=Johnson MB, Criss AK| title=Neisseria gonorrhoeae phagosomes delay fusion with primary granules to enhance bacterial survival inside human neutrophils. | journal=Cell Microbiol | year= 2013 | volume= 15 | issue= 8 | pages= 1323-40 | pmid=23374609 | doi=10.1111/cmi.12117 | pmc=3713093 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23374609  }} </ref>
*Additionally, gonococcus can survive in [[neutrophils]] and [[macrophages]] by preventing the formation of degradative phagolysosomes<ref name="pmid23374609">{{cite journal| author=Johnson MB, Criss AK| title=Neisseria gonorrhoeae phagosomes delay fusion with primary granules to enhance bacterial survival inside human neutrophils. | journal=Cell Microbiol | year= 2013 | volume= 15 | issue= 8 | pages= 1323-40 | pmid=23374609 | doi=10.1111/cmi.12117 | pmc=3713093 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23374609  }} </ref>
*[[cytokines|Inflammatory cytokines]] may release as a result of toxic effect of LOS
*[[cytokines|Inflammatory cytokines]] may be released as a result of toxic effect of LOS
*[[Complement]] activation may result in chemotactic factors release which contributes to [[inflammation]]
*[[Complement]] activation may result in [[chemotactic]] factors release which contributes to [[inflammation]]


===Associated Conditions===
===Associated Conditions===
====HIVinfection====
====HIV infection====
Gonorrhea is associated with increased susceptibility to the transmission and acquisition of [[HIV|HIV infection]] by following mechanisms:<ref name="pmid9217758">{{cite journal| author=Cohen MS, Hoffman IF, Royce RA, Kazembe P, Dyer JR, Daly CC et al.| title=Reduction of concentration of HIV-1 in semen after treatment of urethritis: implications for prevention of sexual transmission of HIV-1. AIDSCAP Malawi Research Group. | journal=Lancet | year= 1997 | volume= 349 | issue= 9069 | pages= 1868-73 | pmid=9217758 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9217758  }} </ref><ref name="pmid8442924">{{cite journal| author=Laga M, Manoka A, Kivuvu M, Malele B, Tuliza M, Nzila N et al.| title=Non-ulcerative sexually transmitted diseases as risk factors for HIV-1 transmission in women: results from a cohort study. | journal=AIDS | year= 1993 | volume= 7 | issue= 1 | pages= 95-102 | pmid=8442924 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8442924  }} </ref><ref name="pmid23733950">{{cite journal| author=Malott RJ, Keller BO, Gaudet RG, McCaw SE, Lai CC, Dobson-Belaire WN et al.| title=Neisseria gonorrhoeae-derived heptose elicits an innate immune response and drives HIV-1 expression. | journal=Proc Natl Acad Sci U S A | year= 2013 | volume= 110 | issue= 25 | pages= 10234-9 | pmid=23733950 | doi=10.1073/pnas.1303738110 | pmc=3690901 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23733950  }} </ref>
Gonorrhea is associated with increased susceptibility to the transmission and acquisition of [[HIV|HIV infection]] by the following mechanisms:<ref name="pmid9217758">{{cite journal| author=Cohen MS, Hoffman IF, Royce RA, Kazembe P, Dyer JR, Daly CC et al.| title=Reduction of concentration of HIV-1 in semen after treatment of urethritis: implications for prevention of sexual transmission of HIV-1. AIDSCAP Malawi Research Group. | journal=Lancet | year= 1997 | volume= 349 | issue= 9069 | pages= 1868-73 | pmid=9217758 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9217758  }} </ref><ref name="pmid8442924">{{cite journal| author=Laga M, Manoka A, Kivuvu M, Malele B, Tuliza M, Nzila N et al.| title=Non-ulcerative sexually transmitted diseases as risk factors for HIV-1 transmission in women: results from a cohort study. | journal=AIDS | year= 1993 | volume= 7 | issue= 1 | pages= 95-102 | pmid=8442924 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8442924  }} </ref><ref name="pmid23733950">{{cite journal| author=Malott RJ, Keller BO, Gaudet RG, McCaw SE, Lai CC, Dobson-Belaire WN et al.| title=Neisseria gonorrhoeae-derived heptose elicits an innate immune response and drives HIV-1 expression. | journal=Proc Natl Acad Sci U S A | year= 2013 | volume= 110 | issue= 25 | pages= 10234-9 | pmid=23733950 | doi=10.1073/pnas.1303738110 | pmc=3690901 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23733950  }} </ref>
*Increased HIV expression and viral production by activation of HIV infected [[CD4]] (transmission)
*Increased [[HIV]] expression and viral production by activation of HIV infected [[CD4]] (transmission)
*Altered HIV specific [[CD8|CD8 cell]] response (acquisition)
*Altered HIV specific [[CD8|CD8 cell]] response (acquisition)
It seems HIV RNA concentrations in [[semen]] is eightfold higher among those with gonococcal urethritis.
 
HIV RNA concentrations in [[semen]] are eightfold higher among those with gonococcal urethritis.


==References==
==References==
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sara Mehrsefat, M.D. [2]

Overview

Gonorrhea is a sexually transmitted disease (STD) caused by Neisseria gonorrhea. It can infect mucus-secreting epithelial cells both in men and women. Established routes of transmission of the Neisseria gonorrhoeae bacterium include vaginal intercourse, rectal intercourse, fellatio, cunnilingus, and perinatal. The main pathogenicity of the Neisseria gonorrhea stems from the ability of its surface pili to attach to the surface of the urethra, fallopian tubes, and endocervix.[1][2][3] Anotehr virulence factor of gonorrhea is porin. The two main porin serotypes include PorB.1A strains (resulting in a disseminated gonococcal infection) and PorB.1B strains (resulting in local genital infections).[4][5][6]

In pregnancy, gonococcus can be transmitted to the fetus at the time of delivery. This results in infection of the conjuctiva. This appears 1 to 4 days after birth as severe discharge with marked swelling and redness of the eyelids and conjunctiva. Additionally, development of disseminated gonococcal infection is the result of Neisserial organisms' dissemination into the blood due to a variety of predisposing factors such as change in PH, pregnancy, menstruation, PorB.1A strains, and complement deficiencies.[7][8][9][10]

Pathophysiology

Gonorrhea is a sexually transmitted disease (STD) that is caused by Neisseria gonorrhea, a gram-negative intracellular diplococcus, oxidase-positive bacterium that utilizes glucose, but not sucrose, maltose, or lactose. It can infect mucus-secreting epithelial cells in both men and women.

Transmission

Established routes of transmission of the Neisseria gonorrhoeae include:

  • Male to female via semen (transmission rate is estimated to be 50%-70% per episode)
  • Female vagina to male urethra (transmission rate is estimated to be 20% per episode)
  • Rectal intercourse
  • Fellatio and, less commonly, cunnilingus can result in pharyngeal gonorrhea
  • Perinatal

Virulence factors

Established virulence factors of Neisseria gonorrhoeae include:

In pregnancy, gonococcus can be transmitted to the fetus at the time of delivery. This results in infection of the conjuctiva. This appears 1 to 4 days after birth as severe discharge with marked swelling and redness of the eyelids and conjunctiva.

Development of disseminated gonococcal infection is the result of Neisserial organisms' dissemination into the blood due to a variety of predisposing factors such as:[7][8][9][10]

  • Host factors
    • Change in pH
      • Pregnancy
      • Menstruation
  • Virulence factors of the organism itself
    • PorB.1A strains
      • Result in serum resistance
  • Failures of the host's immune defenses
    • Complement deficiencies

Host Factors

Host factors play an important role in mediating entry of gonococci into nonphagocytic cells by following methods:[20][21]

  1. N. gonorrhea activates phosphatidylcholine specific phospholipase C and acidic sphingomyelinase and release of diacylglycerol and ceramide
  2. Accumulation of ceramide results in apoptosis
  3. Apoptosis may cause disruption of epithelial integrity
  4. Disturbed epithelium facilitate entry of gonococci into sub epithelial tissue

Associated Conditions

HIV infection

Gonorrhea is associated with increased susceptibility to the transmission and acquisition of HIV infection by the following mechanisms:[23][24][25]

  • Increased HIV expression and viral production by activation of HIV infected CD4 (transmission)
  • Altered HIV specific CD8 cell response (acquisition)

HIV RNA concentrations in semen are eightfold higher among those with gonococcal urethritis.

References

  1. ↑ 1.0 1.1 Sparling PF (1966). "Genetic transformation of Neisseria gonorrhoeae to streptomycin resistance". J Bacteriol. 92 (5): 1364–71. PMC 276432. PMID 4958881.
  2. ↑ 2.0 2.1 Swanson J (1973). "Studies on gonococcus infection. IV. Pili: their role in attachment of gonococci to tissue culture cells". J Exp Med. 137 (3): 571–89. PMC 2139381. PMID 4631989.
  3. ↑ 3.0 3.1 Wolfgang M, Lauer P, Park HS, Brossay L, Hébert J, Koomey M (1998). "PilT mutations lead to simultaneous defects in competence for natural transformation and twitching motility in piliated Neisseria gonorrhoeae". Mol Microbiol. 29 (1): 321–30. PMID 9701824.
  4. ↑ 4.0 4.1 Young JD, Blake M, Mauro A, Cohn ZA (1983). "Properties of the major outer membrane protein from Neisseria gonorrhoeae incorporated into model lipid membranes". Proc Natl Acad Sci U S A. 80 (12): 3831–5. PMC 394146. PMID 6407021.
  5. ↑ 5.0 5.1 Ram S, Cullinane M, Blom AM, Gulati S, McQuillen DP, Monks BG; et al. (2001). "Binding of C4b-binding protein to porin: a molecular mechanism of serum resistance of Neisseria gonorrhoeae". J Exp Med. 193 (3): 281–95. PMC 2195916. PMID 11157049.
  6. ↑ 6.0 6.1 Ram S, McQuillen DP, Gulati S, Elkins C, Pangburn MK, Rice PA (1998). "Binding of complement factor H to loop 5 of porin protein 1A: a molecular mechanism of serum resistance of nonsialylated Neisseria gonorrhoeae". J Exp Med. 188 (4): 671–80. PMC 2213355. PMID 9705949.
  7. ↑ 7.0 7.1 WATRING, WATSON G., and DANIEL L. VAUGHN. "Gonococcemia in pregnancy." Obstetrics & Gynecology 48.4 (1976): 428-430.
  8. ↑ 8.0 8.1 Angulo, Juan M., and Luis R. Espinoza. "Gonococcal arthritis." Comprehensive therapy 25.3 (1999): 155-162.
  9. ↑ 9.0 9.1 Bohnhoff M, Morello JA, Lerner SA (1986). "Auxotypes, penicillin susceptibility, and serogroups of Neisseria gonorrhoeae from disseminated and uncomplicated infections". J Infect Dis. 154 (2): 225–30. PMID 3088132.
  10. ↑ 10.0 10.1 O'Brien JP, Goldenberg DL, Rice PA (1983). "Disseminated gonococcal infection: a prospective analysis of 49 patients and a review of pathophysiology and immune mechanisms". Medicine (Baltimore). 62 (6): 395–406. PMID 6415361.
  11. ↑ Jerse AE, Cohen MS, Drown PM, Whicker LG, Isbey SF, Seifert HS; et al. (1994). "Multiple gonococcal opacity proteins are expressed during experimental urethral infection in the male". J Exp Med. 179 (3): 911–20. PMC 2191399. PMID 8113683.
  12. ↑ Boulton IC, Gray-Owen SD (2002). "Neisserial binding to CEACAM1 arrests the activation and proliferation of CD4+ T lymphocytes". Nat Immunol. 3 (3): 229–36. doi:10.1038/ni769. PMID 11850628.
  13. ↑ Pantelic M, Kim YJ, Bolland S, Chen I, Shively J, Chen T (2005). "Neisseria gonorrhoeae kills carcinoembryonic antigen-related cellular adhesion molecule 1 (CD66a)-expressing human B cells and inhibits antibody production". Infect Immun. 73 (7): 4171–9. doi:10.1128/IAI.73.7.4171-4179.2005. PMC 1168567. PMID 15972507.
  14. ↑ Harvey HA, Jennings MP, Campbell CA, Williams R, Apicella MA (2001). "Receptor-mediated endocytosis of Neisseria gonorrhoeae into primary human urethral epithelial cells: the role of the asialoglycoprotein receptor". Mol Microbiol. 42 (3): 659–72. PMID 11722733.
  15. ↑ Harvey HA, Porat N, Campbell CA, Jennings M, Gibson BW, Phillips NJ; et al. (2000). "Gonococcal lipooligosaccharide is a ligand for the asialoglycoprotein receptor on human sperm". Mol Microbiol. 36 (5): 1059–70. PMID 10844691.
  16. ↑ Spence JM, Clark VL (2000). "Role of ribosomal protein L12 in gonococcal invasion of Hec1B cells". Infect Immun. 68 (9): 5002–10. PMC 101722. PMID 10948117.
  17. ↑ Tsampalas M, Gridelet V, Berndt S, Foidart JM, Geenen V, Perrier d'Hauterive S (2010). "Human chorionic gonadotropin: a hormone with immunological and angiogenic properties". J Reprod Immunol. 85 (1): 93–8. doi:10.1016/j.jri.2009.11.008. PMID 20227765.
  18. ↑ Lin L, Ayala P, Larson J, Mulks M, Fukuda M, Carlsson SR; et al. (1997). "The Neisseria type 2 IgA1 protease cleaves LAMP1 and promotes survival of bacteria within epithelial cells". Mol Microbiol. 24 (5): 1083–94. PMID 9220014.
  19. ↑ Hobbs MM, Sparling PF, Cohen MS, Shafer WM, Deal CD, Jerse AE (2011). "Experimental Gonococcal Infection in Male Volunteers: Cumulative Experience with Neisseria gonorrhoeae Strains FA1090 and MS11mkC". Front Microbiol. 2: 123. doi:10.3389/fmicb.2011.00123. PMC 3119411. PMID 21734909.
  20. ↑ Duncan JA, Gao X, Huang MT, O'Connor BP, Thomas CE, Willingham SB; et al. (2009). "Neisseria gonorrhoeae activates the proteinase cathepsin B to mediate the signaling activities of the NLRP3 and ASC-containing inflammasome". J Immunol. 182 (10): 6460–9. doi:10.4049/jimmunol.0802696. PMC 2722440. PMID 19414800.
  21. ↑ Mosleh IM, Huber LA, Steinlein P, Pasquali C, Günther D, Meyer TF (1998). "Neisseria gonorrhoeae porin modulates phagosome maturation". J Biol Chem. 273 (52): 35332–8. PMID 9857075.
  22. ↑ Johnson MB, Criss AK (2013). "Neisseria gonorrhoeae phagosomes delay fusion with primary granules to enhance bacterial survival inside human neutrophils". Cell Microbiol. 15 (8): 1323–40. doi:10.1111/cmi.12117. PMC 3713093. PMID 23374609.
  23. ↑ Cohen MS, Hoffman IF, Royce RA, Kazembe P, Dyer JR, Daly CC; et al. (1997). "Reduction of concentration of HIV-1 in semen after treatment of urethritis: implications for prevention of sexual transmission of HIV-1. AIDSCAP Malawi Research Group". Lancet. 349 (9069): 1868–73. PMID 9217758.
  24. ↑ Laga M, Manoka A, Kivuvu M, Malele B, Tuliza M, Nzila N; et al. (1993). "Non-ulcerative sexually transmitted diseases as risk factors for HIV-1 transmission in women: results from a cohort study". AIDS. 7 (1): 95–102. PMID 8442924.
  25. ↑ Malott RJ, Keller BO, Gaudet RG, McCaw SE, Lai CC, Dobson-Belaire WN; et al. (2013). "Neisseria gonorrhoeae-derived heptose elicits an innate immune response and drives HIV-1 expression". Proc Natl Acad Sci U S A. 110 (25): 10234–9. doi:10.1073/pnas.1303738110. PMC 3690901. PMID 23733950.


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